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Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 vectors across AAV serotypes combined with a transposon system, we substantially amplified labeling efficacy and accelerated in vivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% by lentivirus, to achieve analysis of over 30,000 cells in one experiment and enable massively parallel in vivo Perturb-seq. Compatible with various phenotypic measurements (single-cell or spatial multi-omics), it presents a flexible approach to interrogate gene function across cell types in vivo, translating gene variants to their causal function.
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Redes Reguladoras de Genes , Análisis de la Célula Individual , Animales , Femenino , Humanos , Ratones , Corteza Cerebral/metabolismo , Corteza Cerebral/citología , Sistemas CRISPR-Cas/genética , Dependovirus/genética , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Vectores Genéticos/metabolismo , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Neuronas/metabolismo , Neuronas/citología , Análisis de la Célula Individual/métodos , Transcriptoma/genética , Línea Celular , Transcripción GenéticaRESUMEN
Cisplatin, a frequently prescribed chemotherapeutic agent, serves as a clinically therapeutic strategy for a broad range of malignancies. Its primary mode of action centers around interference with DNA replication and RNA transcription, thereby inducing apoptosis in cancer cells. Nevertheless, the clinical utility of cisplatin is constrained by its severe adverse effects and the burgeoning problem of drug resistance. Ginsenosides, potent bioactive constituents derived from ginseng, possess an array of biological activities. Recent scientific investigations underscore the substantial amplification of cisplatin's anticancer potency and the mitigation of its harmful side effects when administered concomitantly with ginsenosides. This review aims to explore the underlying mechanisms at play in this combination therapy. Initially, we provide a concise introduction to the cisplatin. Then, we pivot towards illuminating how ginsenosides bolster the anticancer efficacy of cisplatin and counteract cisplatin resistance, culminating in enhanced therapeutic outcomes. Furthermore, we provide an extensive discussion on the reduction of cisplatin-induced toxicity in the kidneys, liver, gastrointestinal tract, nervous system, and ear, accompanied by immune-fortification with ginsenosides. The existing clinical combined use of cisplatin and ginsenosides is also discussed. We propose several recommendations to propel additional research into the mechanisms governing the synergistic use of ginsenosides and cisplatin, thereby furnishing invaluable insights and fostering advancement in combined modality therapy.
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Cisplatino , Ginsenósidos , Neoplasias , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Cisplatino/administración & dosificación , Ginsenósidos/uso terapéutico , Ginsenósidos/farmacología , Ginsenósidos/administración & dosificación , Humanos , Animales , Neoplasias/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificaciónRESUMEN
In the context of the global energy crisis, the development of high-performance heat transport devices within nano scales has become increasingly important. Theoretical discovery and evaluation of novel structures with high performance in thermal conductivity by affordable calculations could provide significant instructions for experimental studies focusing on thermoelectric device development. For 2-dimensional (2D) functional materials, their heat transport efficiency is correlated with their electronic properties and structural features. In this study, we computationally investigated the heat transport within Janus XClO (X = Cr, Ir); its structural and electronic properties were well solved by first-principles calculations. Furthermore, to evaluate thermodynamics stability and applicability, ab initio molecular dynamics (AIMD) simulations are conducted. Through a benchmarking study upon these XClO monolayers with different compositions, we noticed that their heat transport efficiency is associated with the percentage of doped magnetic atoms. The theoretical insights provided by this study are highly instructive for future experimental studies focusing on thermal device development.
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The poor light absorption and low carrier separation efficiency of Titanium dioxide (TiO2) limit its further application. The introduction of plasma metal Ag have the potential to solve these drawbacks owing to its plasma resonance effect. Thus core-shell structure Ag@TiO2 plasma photocatalysts was prepared by using facile reduction method in this work. More specifically, Ag@TiO2 composite catalysts with different Ag loading amounts were prepared in the presence of surfactant PVP. Ag@TiO2 demonstrates excellent light absorption performance and photoelectric separation efficiency compared with pure TiO2. As a result, it displays excellent performance of Cr(VI) reduction under visible light. The optimal composite catalysts Ag@TiO2-5P achieves exceptional visible-light-driven photocatalytic Cr(VI) reduction efficiency of 0.01416 min-1 that is 2.29 times greater than pure TiO2. To investigate the role of PVP, we also synthesized Ag@TiO2-5 without PVP. The experimental results show that although Ag@TiO2-5 Cr(VI) reduction performance is superior to pure TiO2, it significantly decreases compared with Ag@TiO2-5P. The results of TEM and optoelectronic testing show that agglomeration of Ag particles leads to a decrease in the photoelectric separation efficiency of Ag@TiO2-5. The smaller Ag particles provide more active sites and demonstrating a stronger overall local surface plasmon resonance (LSPR) effect. DMPO spin-trapping ESR spectra testing indicates that âO2- and âOH are the main reactive species. This research provides a potential strategy to prepare Ag-based plasma photocatalysts for environment protection.
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Plata , Resonancia por Plasmón de Superficie , Plata/química , Titanio/química , Cromo/química , Luz , CatálisisRESUMEN
The manipulation of soil pH through liming and straw incorporation plays a pivotal role in influencing soil organic carbon (SOC) dynamics in acidic red soil. This study aimed to assess the impact of these practices on SOC and elucidate the relationship between SOC and pH. Over a 31-year field experiment, seven different fertilization treatments were implemented: unfertilized (CK), nitrogen and potassium fertilizers (NK), NK with lime (NKCa), nitrogen, phosphorous, and potassium fertilizers (NPK), NPK with lime (NPKCa), NPK with straw (NPKS), and NPKS with lime (NPKSCa). Results revealed that liming and straw incorporation significantly elevated soil pH by 0.13-0.73 units. Lime application boosted SOC and mineral-associated organic carbon (MAOC) by 20.2% and 28.7%, respectively, in NK treatment, whereas its impact on SOC in NPK and NPKS treatments were negligible. SOC witnessed a 17.1% increase with NPKS and a 15.2% increase with NPKSCa compared to NPK alone. Notably, NPKS and NPKSCa led to a significant surge in particulate organic carbon (POC) by 19.7% and 37.7%, respectively, albeit NPKSCa reduced MAOC by 14.9% relative to NPK. Linear regression analysis unveiled a positive correlation between POC and soil pH, while SOC and MAOC exhibited an initial rise at lower pH levels followed by stabilization as pH continuously increasing. A partial least squares path model showed two pathways through which pH influenced SOC: firstly, by positively affecting SOC through increasing Fe and Al oxides contents and enhanced aggregate stability, and secondly, by negatively influencing SOC through altered ratios of fungi/bacteria and Gram-positive bacteria/Gram-negative bacteria. In conclusion, the long-term effects of lime and straw application on SOC and MAOC were contingent upon soil pH, with more pronounced positive effects observed at lower pH levels. These findings underscore the importance of considering soil pH when implementing lime and straw strategies to mitigate acidification and regulate SOC in acidic red soil.
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Carbono , Fertilizantes , Suelo , Suelo/química , Carbono/química , Concentración de Iones de Hidrógeno , Fertilizantes/análisis , Óxidos/química , Compuestos de Calcio/química , Nitrógeno/química , Potasio/química , Potasio/análisisRESUMEN
A mathematical description and experimental outputs exhibited that an ion chronogram from an in-tube solid-phase microextraction (SPME) device linked with mass spectrometry (in-tube-SPME-MS) generally appears as a right-skew unimodal signal with a heavy right tail. Analogous to liquid chromatography coupled with mass spectrometry (LC-MS), in-tube-SPME-MS can utilize the area under its produced ion chronogram for regression analysis and has been shown to be a potential approach for fast quantification of analyte. Different level of unimodity of signal in the ion chronogram could positively or negatively affect the choice of the area used for quantification and finally impact on analysis sensitivity and time efficiency of in-tube-SPME-MS. In the paper, we showed that different in-tube SPME design choices and elution experimental setups produce ion chronograms with controllable varying unimodal peak shape patterns. An improved mathematical model was built based on the plate theory of chromatography and the Van Deemter equation to quantitatively describe the elution process from in-tube-SPME device. A computer simulation was implemented to predict ion chronograms and the results were compared with experimental ion chronograms to show the effectiveness of the model. An optimization framework was further presented based on the model to identify optimal device designs (length and diameter of device) and experimental parameters (flow rate) to track targeted ion chronograms with "desired" peak shape patterns. Empirical elution experiments with the in-tube SPME devices adopting optimized geometric parameters and optimal experimental setups confirmed the consistency between the experimental ion chronograms and the numerical simulations to a certain level.
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Modelos Teóricos , Extracción en Fase Sólida , Extracción en Fase Sólida/instrumentación , Extracción en Fase Sólida/métodos , Iones/química , Espectrometría de Masas/instrumentación , Espectrometría de Masas/métodos , Modelos LinealesRESUMEN
Herein, a practical method for the determination of organic and inorganic Cl in gaseous ethylene by liquid standard samples was established; and then, the effects of various speciation and matrices on results were investigated followed by automatic quick furnace-ion chromatography (AQF-IC) analysis. From the evaluation of speciation and matrices, unified equation was explored and the method for accurately determining trace HCl with strong adsorption was also developed. First, summarize regularity that the light oil liquid standards themselves conformed to equal Cl mass response by AQF-IC (R2=0.99993). Then, the actual Cl mass in standard gas at 4 levels with different speciation and matrices were calculated by the same regularity based on the assumption of not affected by speciation or matrix change. The gas mass was accurately calculated based on Van der Waals' Equation. As a result, combined with the theoretical Cl mass calculated by equation, the recoveries of the organic and inorganic Cl were in the range of 93.0%-101.4% [2.0 µmol/mol of CH3Cl/(N2+ethylene)], 93.4%-104.9% (10.1 µmol/mol of CH3Cl/N2), 101.6%-111.2% (20.2 µmol/mol of CH3Cl/ethylene) and 95.3%-101.0% (11.0 mg/m3 of HCl/N2), respectively, indicating the successful verification of above assumption rather than applying more exploration to rebuild relationships between different systems. As proof of principle and for more verification, system of CH2Cl2/He gas standard sample was prepared to explore the quantitative accuracy in more speciation with recoveries in the range of 91.3%-98.5%. In addition, the detection limit of Cl content based on S/N = 3 for ethylene was 0.06 mg/kg. Intra-day and inter-day relative standard devations (RSDs) were in the range of 9.3%-12.0% (≤1.0 mg/kg) and 2.5%-4.4% (>1.0 mg/kg). Finally, the developed method based on gas-liquid equal mass response was successfully applied in the actual samples of light olefins such as ethylene and propylene.
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Gases , Agua , Agua/química , Cromatografía , Iones , EtilenosRESUMEN
Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in the progression of Parkinson's disease (PD), but the specific regulatory role needs further exploration. This study showed that the expression of NEAT1 was upregulated in the cerebrospinal fluid (CSF) and peripheral blood of patients with different stages of PD. 1-Methyl-4-phenylpyridine (MPP)-treated PC 12 cells were transfected with si-NEAT1, and MPP treatment promoted cell apoptosis, oxidative stress and inflammatory factor secretion. Si-NEAT1 reversed the effects of MPP. NEAT1 silencing eliminated the effect of MPP on the protein expression levels of LC3-II and p62/SQSTM1. By using an online bioinformatics database, Fused in Sarcoma (FUS) was confirmed to be an RNA binding protein of NEAT1, and it was highly expressed in the CSF and peripheral blood of patients with PD. Si-FUS was transfected into MPP-treated PC 12 cells to detect cell apoptosis, oxidative stress, inflammatory factor secretion and autophagy, and the results were the same as those of transfection of si-NEAT1. Furthermore, MPP treatment reduced the phosphorylation levels of PI3K, Akt and mTOR, whereas si-FUS reversed the effects of MPP. In vivo, compared with the model group, the PD mice showed reduced NEAT1 and FUS expression levels and activated PI3K pathway after being injected with si-NEAT1. The brain tissue of NEAT1-silenced PD mice had decreased inflammatory infiltration and apoptosis and increased neurological scores. In conclusion, NEAT1 is involved in PD progression through FUS-mediated inhibition of the PI3K/AKT/mTOR signalling pathway.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Largo no Codificante , Proteína FUS de Unión a ARN , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteína FUS de Unión a ARN/genética , Proteína FUS de Unión a ARN/metabolismo , Células PC12 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Humanos , Apoptosis , Progresión de la Enfermedad , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Ratones Endogámicos C57BL , Estrés Oxidativo , 1-Metil-4-fenilpiridinio , AutofagiaRESUMEN
Modern solid phase microextraction (SPME) device linked with mass spectrometry (SPME-MS) has evolved from producing ion chronogram as flat noisy signal to as unimodal-like signal. We designed a SPME device, which is closer in morphology to LC column, linked it with a miniature mass spectrometer (SPME-Mini MS), and proposed a mathematical model that elution of compound from the SPME device is equivalent to overlay of elution of the compound from the infinite LC columns with the lengths between 0 and the length of the device and it can generate an ion chronogram as right-skew unimodal signal. Rhodamine B as analyte was used for experimental verification and its unimodal signal was used to fit the parameters of a computer simulation program based on the model. The experimental results and simulations empirically cross-confirmed that SPME-Mini MS can generate ion chronogram as clean right-skew unimodal signal. Furthermore, the SPME-Mini MS system was used for quantitative analysis of psychotropic drugs (i.e. risperidone and aripiprazole) in artificial urine. The results preliminarily demonstrated that the system can utilize area under unimodal signal for quantitative analysis and has potential to be applied for on-site, fast and accurate quantification of drugs and other compounds.
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Self-ambivalence, a prevalent phenomenon in daily life, has been increasingly substantiated by research. It refers to conflicting self-views and evaluations, primarily concerning self-worth and morality. Previous behavioral research has distinguished self-worth and moral ambivalence, but it remains unclear whether they have separable neural bases. The present study addressed this question by examining resting-state brain activity (i.e., the fractional amplitude of low-frequency fluctuations, fALFF) and connectivity (i.e., resting-state functional connectivity, RSFC) in 112 college students. The results found that self-worth ambivalence was positively related to the fALFF in the orbitofrontal cortex (OFC) and left superior parietal lobule (SPL). The RSFC strength between the SPL and precuneus/posterior cingulate cortex (PCC) was positively related to self-worth ambivalence. Moral ambivalence was positively associated with the fALFF in the left SPL (extending into the temporoparietal junction) and right SPL. The RSFC strengths between the left SPL/TPJ and OFC, as well as the RSFC strengths between the right SPL as a seed and the bilateral middle and inferior temporal gyrus, were associated with moral ambivalence. Overall, the neural bases of self-worth and moral ambivalence are associated with the SPL and OFC, involved in attentional alertness and value representation, respectively. Additionally, the neural basis of moral ambivalence is associated with the TPJ, responsible for mentalizing.
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Cucumber wilt is an important soil borne disease in cucumber production, which seriously affects the development of the cucumber industry. Cleome spinosa also has pharmacological effects such as antibacterial, analgesic, anti-inflammatory, and insect repellent. To study the control effect and mechanism of Cleome spinosa fumigation on cucumber wilt disease, different concentrations of Cleome spinosa fragments were applied on cucumber plants infected with Fusarium oxysporum. Cleome spinosa fumigation significantly reduced the incidence rate of cucumber Fusarium wilt. Under the fumigation treatment of 7.5 g kg-1 Cleome spinosa fragments, the preventive effects were 74.7%. Cleome spinosa fragments fumigation can promote cucumber growth and synthesis of photosynthetic pigments, thereby improving individual plant yield and fruit quality. At 7.5 g kg-1 Cleome spinosa fragments fumigation treatment, the plant height and individual plant yield of cucumber increased by 20.3% and 34.3%, respectively. Cleome spinosa fumigation can enhance the activity of antioxidant enzymes in cucumber, maintain a balance of reactive oxygen species metabolism, and enhance the plant disease resistance. Moreover, Cleome spinosa can also regulate the activities of Mg2+-ATPase and Ca2+-ATPase, enhancing its resistance to Fusarium oxysporum. Moreover, number of bacteria and fungi significantly decreased under Cleome spinosa fumigation. Those results suggested that Cleome spinosa could effectively restrain cucumber Fusarium wilt. This study will provide a new idea for the further use of biological fumigation to prevent soil-borne diseases.
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The efficient management of fertilizer application in agriculture is vital for both food security and mitigating greenhouse gas (GHG) emissions. However, as potassium fertilizer (KF) is an essential soil nutrient, its impact on soil GHG emissions has received little attention. To address this knowledge gap and identify key determinants of GHG emissions, we conducted a comprehensive meta-analysis of 205 independent experiments conducted worldwide. Our results revealed that, in comparison to sole nitrogen fertilizer (NF) application, the concurrent use of KF elevated nitrous oxide (N2O) and methane (CH4) emissions by 39.5 % and 21.1 %, respectively, while concurrently reducing carbon dioxide (CO2) emissions by 8.1 %. The ratio of nitrogen and potassium fertilizer input (NF/KF) is identified as the primary factor explaining the variation in N2O emissions, whereas the type of KF plays a crucial role in determining CH4 and CO2 emissions. We observed a significant negative correlation between the NF/KF ratio and response ratios of N2O and CH4 emissions and a positive correlation with CO2 emissions response ratios. Furthermore, our findings indicate that when the NF/KF ratio surpasses 1.97, 4.61, and 3.78, respectively, the impact of KF on reducing N2O, CH4, and CO2 emissions stabilizes. Overall, our results underscore that the global integration of KF into agricultural practices significantly influences N2O and CH4 emissions, while simultaneously reducing CO2 emissions at a large scale. These findings provide a foundational framework and practical guidance for optimizing fertilizer application in the development of GHG emission reduction models.
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The improvement in the agricultural production through continuous and heavy nutrient input like nitrogen fertilizer under the upland red soil of south China deteriorates soil quality, and this practice in the future could threaten future food production and cause serious environmental problems in China. This research is initiated with the objectives of evaluating the impacts of long-term chemical nitrogen fertilization on soil quality, crop yield, and greenhouse gas emissions, with insights into post-lime application responses. Compared to sole application of chemical nitrogen fertilization, combined application with lime increased soil indicators (pH by 6.30 %-7.76 %, Ca2+ by 90.06 %-252.77 %, Mg2+ by 184.47 %-358.05 %, available P by 5.05 %-30.04 %, and soil alkali hydrolysable N by 23.49 %-41.55 %. Combined application of chemical nitrogen fertilization with lime (NPCa (0.59), NPKCa (0.61), and NKCa (0.27) significantly improved soil quality index compared to the sole application of chemical nitrogen fertilization (NP (0.31), NPK (0.36), and NK (0.16). Compared to sole application of chemical nitrogen fertilization, combined application with lime increased grain yield by 48.36 %-61.49 %. Structural equation modeling elucidated that combined application of chemical nitrogen fertilization and lime improved wheat grain yield by improving soil quality. Exchangeable Ca2+, exchangeable Mg2+, pH, and exchangeable Al3+ were the most influential factors of wheat grain yield. Overall, the combined application of chemical nitrogen fertilization and lime decreased global warming potential (calculated from N2O and CO2) by 16.92 % emissions compared to the sole application of chemical nitrogen fertilization. Therefore, liming acidic soil in upland red soil of South China is a promising management option for improved soil quality, wheat grain yield, and mitigation of greenhouse gas emissions.
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Background and objectives: Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease. Materials and methods: This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods. Results: By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study. Conclusion: This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.
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BACKGROUND: Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account. METHODS: Depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). HAMD-17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)-logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis. RESULTS: The rate of depressive symptom in patients with PBC (n = 162) was higher than in healthy controls (n = 180) (52.5% vs. 16.1%; p < .001). HAMD-17 score was negatively associated with C4 levels and positively associated with levels of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TB), Immunoglobulin (Ig) G, and IgM (r = -0.162, 0.197, 0.355, 0.203, 0.182, 0.314, p < .05). In Lasso-logistic regression analysis, HAMD-17 score, human leukocyte antigen (HLA)-DRB1*03:01 allele, age, ALP levels, and IgM levels (odds ratio [OR] = 1.087, 7.353, 1.075, 1.009, 1.005; p < 0.05) were independent risk factors for cirrhosis. Elevated HAMD-17 score was also a discriminating factor for high risk of cirrhosis in patients with PBC in decision tree model. CONCLUSIONS: Depressive symptoms were associated with disease severity. Elevated HAMD-17 score was a risk factor for cirrhosis in patients with PBC.
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Árboles de Decisión , Depresión , Cirrosis Hepática Biliar , Humanos , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , Depresión/epidemiología , Depresión/etiología , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/epidemiología , Modelos Logísticos , Anciano , Adulto , Cirrosis Hepática/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiologíaRESUMEN
Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide1-6. Clinical studies have demonstrated that the severity of cardiac injury following myocardial infarction exhibits a circadian pattern, with larger infarct sizes and poorer outcomes in patients experiencing morning onset myocardial infarctions7-14. However, the molecular mechanisms that govern circadian variations of myocardial injury remain unclear. Here, we show that BMAL114-20, a core circadian transcription factor, orchestrates diurnal variability in myocardial injury. Unexpectedly, BMAL1 modulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with a non-canonical partner, hypoxia-inducible factor 2 alpha (HIF2A)6,21-23, in a diurnal manner. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2A/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1, which enables the crosstalk between circadian rhythms and hypoxia signaling. Furthermore, we identified amphiregulin (AREG) as a rhythmic transcriptional target of the BMAL1/HIF2A heterodimer, critical for regulating circadian variations of myocardial injury. Finally, pharmacologically targeting the BMAL1/HIF2A-AREG pathway provides effective cardioprotection, with maximum efficacy when aligned with the pathway's circadian trough. Our findings not only uncover a novel mechanism governing the circadian variations of myocardial injury but also pave the way for innovative circadian-based treatment strategies, potentially shifting current treatment paradigms for myocardial infarction.